Barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.] is a problematic weed that grows in rice (Oryza sativa L.) fields. Over-applying herbicide caused environmental pollution and the emergence of resistant weeds, and integrated weed management method can reduce the dependence on herbicides. The growth of E. crus-galli and rice seedlings could be significantly inhibited by high concentrations of fulvic acid (FA, C14H12O8) under flooding conditions (HF, 0.80 g/L) (p < 0.05). In contrast, the growth of seedlings could be promoted by the application of very low-concentration FA (LF, 0.02 g/L). The activities of glutathione S-transferase (GSTs) and antioxidant enzymes, including total superoxide dismutase (T-SOD), peroxidase (POD), and catalase (CAT) in E. crus-galli seedlings were enhanced by LF treatment; while the POD activity was decreased, the GSTs, T-SOD, and CAT activities were not significantly changed by HF treatment. The metabolomic and transcriptomic analyses showed that FA regulated E. crus-galli seedling growth by affecting the synthesis of indole derivatives and flavonoid compounds. Compared with the blank control (CK, 0 g/L), the levels of four indole derivatives were up-regulated under HF treatment, and the indole derivatives mentioned above were slightly down-regulated under LF treatment. The flavonoids, including naringenin, naringenin chalcone, eriodictyol, kaempferol, and epigallocatechin, were down-regulated under HF treatment, and the growth of E. crus-galli was restrained. In contrast, the metabolism and transcription of flavonoids were not significantly changed under LF treatment. Under the addition of 0.80 g/L FA, the growth of newly sprouted E. crus-galli was obviously inhibited, and the growth of rice was significantly promoted after eight days of rice planting (p < 0.05). The application of FA, therefore, might be a potential integrated weed management method to control the damage caused by E. crus-galli in paddy fields.